Project description:Analysis of Foxd3-regulation of self-renewal and quiescence in CDCP1+CSCs at gene expression level. The hypothesis tested in the present study was that the Foxd3 global developmental regulator serves a critical role to support the self-renewal of CDCP1+CSCs as one of few known factors involved in maintaining their quiescence. Results provide important information of the response of colorectal CDCP1+CSCs to depletion of Foxd3, such as genes involved in regulation of cell cycle, cell proliferation, and stem-like properties.
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
